Epigenetics: how the environment changes our genes!

Epigenetics: the environment that changes our genes!

It took almost half a century between the discovery of the structure of DNA in 1953 and the first almost complete mapping of the human genome in 2001. Dreaded by this extraordinary scientific advance, many researchers succumbed at the beginning of this century to the "dictatorship of the genome".

It seemed reasonable to think that from the moment we finally knew the location and role of the 25,000 genes that make up our genome, we could explain and heal by means of genetics most of the major pathologies that affect us, whether it is cancer, cardiovascular diseases, metabolic diseases or neurodegenerative diseases such as Parkinson's or Alzheimer's.

But for the last ten years, scientists have gone from surprise to surprise and discovered that not only the same genes did not seem to work in the same way, but the very structure of our genome could be modified, either transiently or permanently, under the effect of the environment: epigenetics was born.

We will not go into detail here about the extremely complex and subtle mechanisms that allow these profound, transitory or definitive modifications of our genes under the pressure of the environment. Recall that, for the record, these modifications may use several pathways, the main ones being histone modifications, DNA methylation and non-coding RNAs.

Remarkably, it seems that a multitude of environmental factors, physical activity, diet, stress, meditation, are able to transform, sometimes irreversibly, not only the functioning but also the structure of some of our genes.

Recently, US researchers at Oregon State University have shown that regular consumption of a compound called sulforaphane (found in some cabbages, including broccoli) may activate the expression of a gene called "Tumor suppressor" and thus prevent the development of certain cancers (colon and prostate). This study is all the more interesting as it also shows that this epigenetic effect seems to persist for a long time even if the subjects stop consuming sulphoraphane (see Clinical Epigenetics).

As Susie Mossman Riva, a doctor of social sciences and researcher at the La Source University of Health in Lausanne, points out, "It is up to us to make the most of our genetic capital by opting for a healthy lifestyle, focused on a balanced diet, regular physical activity and intense social life. "

A few weeks ago, a new study confirmed this influence of the environment on our genes by showing in animals that the life choices of future fathers could influence the lives of their offspring (see Science).

This research has shown that the administration of ethanol to male mice affects the epigenetic signatures of the brain of their offspring over several generations and it is likely that the equivalent epigenetic mechanisms are at work in humans ...

At the beginning of 2015, an international research team published the most comprehensive data available to date on the human epigenome. Presented as the "first exhaustive map of the epigenome of a large number of human cells", these data have been grouped together in some twenty published studies, as part of the Epigenomics program, in the prestigious journal Nature.

These studies have described the epigenome of 111 types of cardiac, muscle, liver, dermatological and fetal cells. This work reminds us that our genes represent only 1.5% of the human genome. The rest, called "junk DNA" has long been considered to have no particular function, but it is now known that this "junk DNA" plays an essential role, via epigenetic mechanisms, in the regulation of gene activity.

"This is a major breakthrough in the ongoing efforts to understand how the three billion letters in an individual's DNA book can result in very diverse molecular activities," notes Francis Collins, head of the American National Institute of Health (NIH). William Cockson, a professor at Imperial College London, believes that "the way genes are read is probably much more important than the genetic code itself."

But what is true at the level of an individual is also true at the level of a population, as just shown by a fascinating study carried out by the CNRS and the Pasteur Institute. In this work, researchers have tried to understand how the human species manages to adapt to sometimes abrupt changes in its environment, for example in terms of climate,

This research, led by Luis Quintana-Murci, showed that these different types of changes in the living conditions of human populations can also act at the epigenetic level, by modifications modulating the expression of genes. To measure the influence of the environment on the epigenome, the researchers worked on the comparative analysis of two Central African populations with different lifestyles and habitats: the Pygmies, a nomadic hunter-gatherer people living in the forest, and the Bantu, settled farmers in urban, rural or forest habitats.

The researchers compared the level of genomic methylation of this population of forest Bantu with that of urban or rural Bantu. They observed that the recent habitat change has caused changes in the epigenome mainly concerning the functions of the immune system. The scientists also compared the methylations of the Bantu forest group with those of the Pygmies to study the impact of their lifestyle on their genome. They then noted differences in the epigenome, this time related to development (size, bone mineralization).

This research finally showed that the most recent changes in the epigenome that affect immunity were devoid of genetic control, whereas the oldest epigenetic differences, which can be described as "historical", were become heritable, stable and transmittable, which illuminates with a new light the appearance of predispositions to diseases.

In conclusion, Luis Quintana-Murci states "Our study shows that changes in lifestyle and habitat strongly influence our epigenome, and that urbanization has a significant impact on the epigenetic profiles of the immune system, which confirms the major role of epigenetic changes in the development of many pathologies, autoimmune diseases, allergies, inflammations ... "

Epigenetics is also shaking up and expanding the scientific and conceptual grids of understanding cancer. It is known, for example, that the BRCA1 mutation inherited from a parent causes at least 10% of breast cancer cases, but the causes involved in the remaining 90% of cancer are unknown.

Another study led by Semira Gonseth, at the University of California at San Francisco and published a few days ago in the journal "Epigenetics" (see Taylor & Francis online) showed, from DNA analysis of 347 healthy children, that some epigenetic modifications were implicated in the development of a very rare blood cancer in children.

This study has shown that the consumption of certain vitamins, especially folic acid (vitamin B9) by expectant mothers, played a key role in triggering certain epigenetic mechanisms that could prevent the appearance of this cancer of the blood. "It may be that folic acid protects the unborn child from adverse epigenetic changes that can also cause cancer," says Semira Gonseth.

Lastly, a study conducted in 2013 by a California team from the Salk Institute for Biological Studies in collaboration with the University of Barcelona. This work, led by Joseph R. Ecker, showed how the activation or extinction of certain genes via DNA methylation (one of the main epigenetic mechanisms) plays a central role during childhood and adolescence. the construction and enrichment of the synaptic communication network in our brain (see Medical Xpress).

To obtain these results, the researchers compared exact methylation sites throughout the cerebral genome at different ages, in newborns, 16-year-olds, and 25- to 50-year-old adults. Researchers have discovered that there is a form of methylation in neurons and glia from birth. They also highlighted the presence of another form of methylation that appears to be at work only in the process of interconnecting neurons that accompany brain maturation of the child and adolescent.

These discoveries not only provide a better understanding of the quite remarkable mechanism of brain plasticity that allows us to learn and adapt to changing situations throughout our lives, but also opens new avenues for understanding the biological bases of certain psychiatric pathologies which require the meeting of a genetic predisposition and a set of particular environmental factors.

As Ryan Lister, one of the researchers involved in this study, points out, "The human brain is considered to be the most complex object known in the Universe and so we should not be surprised that this complexity extends to the level of the epigenome of the brain. These unique features of DNA methylation that emerge during the critical phases of brain development suggest the presence of a powerful epigenetic mechanism that is not only necessary for the proper functioning of our brain but is very likely to be involved in many psychiatric conditions. "

All these decisive advances in this largely unexplored field of epigenetics render the old scientific and ideological opposition between genetic causes and environmental factors, both innate and acquired, to be obsolete. We now know that the power of our genes, if it can not be denied, can be understood and meaningful only in the conceptual framework of a dynamic and permanent interaction with the myriad factors that make up our environment.

Far from determining us and reducing us to a reductive and predictable biological dimension, our genes paradoxically become the framework for the unfolding of our freedom. They translate the stable but modifiable and adaptable biological expression, according to certain laws which are beginning to be clarified, of our individual behaviors and of our evolution, both within our species and our human societies, rich of their abundant and irreplaceable diversities.

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Written by @Bitxx

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